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  Elevated MACC1 Expression in Colorectal Cancer Is Driven by Chromosomal Instability and Is Associated with Molecular Subtype and Worse Patient Survival

Vuaroqueaux, V., Musch, A., Kobelt, D., Risch, T., Herrmann, P., Burock, S., et al. (2022). Elevated MACC1 Expression in Colorectal Cancer Is Driven by Chromosomal Instability and Is Associated with Molecular Subtype and Worse Patient Survival. Cancers / Molecular Diversity Preservation International (MDPI), 14(7): 1749. doi:10.3390/cancers14071749.

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Cancers_Vuaroqueaux et al_2022.pdf (Publisher version), 5MB
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Cancers_Vuaroqueaux et al_2022.pdf
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© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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 Creators:
Vuaroqueaux, Vincent, Author
Musch, Alexandra , Author
Kobelt, Dennis , Author
Risch, Thomas1, Author              
Herrmann, Pia, Author
Burock, Susen , Author
Peille, Anne-Lise , Author
Yaspo, Marie-Laure1, Author              
Fiebig, Heinz-Herbert, Author
Stein, Ulrike, Author
Affiliations:
1Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2117287              

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Free keywords: CRC; MACC1; gene copy number alteration; gene expression; survival
 Abstract: Metastasis-Associated in Colon Cancer 1 (MACC1) is a strong prognostic biomarker inducing proliferation, migration, invasiveness, and metastasis of cancer cells. The context of MACC1 dysregulation in cancers is, however, still poorly understood. Here, we investigated whether chromosomal instability and somatic copy number alterations (SCNA) frequently occurring in CRC contribute to MACC1 dysregulation, with prognostic and predictive impacts. Using the Oncotrack and Charité CRC cohorts of CRC patients, we showed that elevated MACC1 mRNA expression was tightly dependent on increased MACC1 gene SCNA and was associated with metastasis and shorter metastasis free survival. Deep analysis of the COAD-READ TCGA cohort revealed elevated MACC1 expression due to SCNA for advanced tumors exhibiting high chromosomal instability (CIN), and predominantly classified as CMS2 and CMS4 transcriptomic subtypes. For that cohort, we validated that elevated MACC1 mRNA expression correlated with reduced disease-free and overall survival. In conclusion, this study gives insights into the context of MACC1 expression in CRC. Increased MACC1 expression is largely driven by CIN, SCNA gains, and molecular subtypes, potentially determining the molecular risk for metastasis that might serve as a basis for patient-tailored treatment decisions.

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Language(s): eng - English
 Dates: 2022-03-282022-03-29
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.3390/cancers14071749
 Degree: -

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Title: Cancers / Molecular Diversity Preservation International (MDPI)
  Abbreviation : Cancers (Basel)
Source Genre: Journal
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Publ. Info: Basel : Molecular Diversity Preservation International (MDPI)
Pages: - Volume / Issue: 14 (7) Sequence Number: 1749 Start / End Page: - Identifier: ISSN: 2072-6694
CoNE: https://pure.mpg.de/cone/journals/resource/2072-6694